Description:
<jats:title>Abstract</jats:title><jats:p>The Y‐box‐binding protein (<jats:styled-content style="fixed-case">YB</jats:styled-content>)‐1 plays a non‐redundant role in both systemic and local inflammatory response. We analysed <jats:styled-content style="fixed-case">YB</jats:styled-content>‐1‐mediated expression of the immune regulatory cytokine <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 in both <jats:styled-content style="fixed-case">LPS</jats:styled-content> and sterile inflammation induced by unilateral renal ischaemia–reperfusion (I/R) and found an important role of <jats:styled-content style="fixed-case">YB</jats:styled-content>‐1 not only in the onset but also in the resolution of inflammation in kidneys. Within a decisive <jats:italic>cis</jats:italic>‐regulatory region of the <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>10</jats:italic> gene locus, the fourth intron<jats:italic>,</jats:italic> we identified and characterized an operative <jats:styled-content style="fixed-case">YB</jats:styled-content>‐1 binding site <jats:italic>via</jats:italic> gel shift experiments and reporter assays in immune and different renal cells. <jats:italic>In vivo</jats:italic>,<jats:styled-content style="fixed-case"> YB</jats:styled-content>‐1 phosphorylated at serine 102 localized to the fourth intron, which was paralleled by enhanced <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression in mice following <jats:styled-content style="fixed-case">LPS</jats:styled-content> challenge and in I/R. Mice with half‐maximal expression of <jats:styled-content style="fixed-case">YB</jats:styled-content>‐1 (<jats:italic>Yb1</jats:italic><jats:sup><jats:italic>+/−</jats:italic></jats:sup>) had diminished <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 expression upon <jats:styled-content style="fixed-case">LPS</jats:styled-content> challenge. In I/R, <jats:italic>Yb1</jats:italic><jats:sup><jats:italic>+/−</jats:italic></jats:sup> mice exhibited ameliorated kidney injury/inflammation in the early‐phase (days 1 and 5), however showed aggravated long‐term damage (day 21) with increased expression of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 and other known mediators of renal injury and inflammation.</jats:p><jats:p>In conclusion, these data support the notion that there are context‐specific decisions concerning <jats:styled-content style="fixed-case">YB</jats:styled-content>‐1 function and that a fine‐tuning of <jats:styled-content style="fixed-case">YB</jats:styled-content>‐1, for example, <jats:italic>via</jats:italic> a post‐translational modification regulates its activity and/or localization that is crucial for systemic processes such as inflammation.</jats:p>